1. Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.
- Author
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Sacha CR, Vandergrift N, Jeffries TL Jr, McGuire E, Fouda GG, Liebl B, Marshall DJ, Gurley TC, Stiegel L, Whitesides JF, Friedman J, Badiabo A, Foulger A, Yates NL, Tomaras GD, Kepler TB, Liao HX, Haynes BF, Moody MA, and Permar SR
- Subjects
- Black or African American, Antibody Formation immunology, B-Lymphocytes cytology, CD4 Lymphocyte Count, Clonal Evolution, Colostrum cytology, Complementarity Determining Regions genetics, Epitopes, B-Lymphocyte immunology, Female, HIV Antibodies immunology, HIV Envelope Protein gp41 immunology, HIV Infections blood, HIV Infections transmission, HIV Infections virology, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Immunologic Memory, Immunophenotyping, Infectious Disease Transmission, Vertical, Mutation Rate, Phenotype, Somatic Hypermutation, Immunoglobulin, Viral Load, B-Lymphocytes immunology, B-Lymphocytes metabolism, Colostrum immunology, HIV Envelope Protein gp120 immunology, HIV Infections genetics, HIV Infections immunology, HIV-1 immunology, Lactation
- Abstract
A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.
- Published
- 2015
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